Since the beginning of antiquity those engaged in pharmacy and medicine have sought a dosage form designed as a delivery system for the controlled administration of a beneficial agent to an environment of use. The first written reference to a delivery system, a dosage form, is in the Eber Papayrus written about 1552 B. C. The Eber Papayrus mentions dosage forms such as anal suppositories, vaginal pessaries, ointments, oral pill formulations and other dosage preparations. About 2500 years passed without any advance in dosage form development until the Arab physician Rhazes, 865-925 A. D., invented the coated pill. About a century later the Persian Avicenna, 980-1037 A. D., coated pills with gold or silver for increasing patient acceptability and for enhancing the effectiveness of the drug. Also around this time the first tablet was described in Arabian manuscripts written by Al-Zahrawi, 936-1009 A. D. The manuscripts described a tablet formed from the hollow impressions in two matched, facing tablet molds. Pharmacy and medicine waited about 800 years for the next innovation in dosage forms when in 1883 Mothes invented the capsule for administering a drug. The next quantum and profound leap in dosage forms came in 1972 with the invention of the osmotic delivery device invented by Theeuwes and Higuchi. This unique osmotic delivery device is manufactured in one embodiment for oral use. In this embodiment, it embraces the appearance of a tables comprising an internal drug core and a delivery portal. After a start-up period, it delivers drug at a controlled rate over a prolonged period of time. It is the first oral dosage form that delivers a drug throughout the entire gastrointestinal tract in a controlled dose per unit time.
While the above described osmotic system comprising a single drug core represents an outstanding and pioneering advancement in the osmotic delivery art, and while the osmotic system is useful for dispensing innumerable drugs to the environment of use, it has now been
ARC 1393 discovered that these osmotic systems can be improved further to enhance the delivery kinetics and the usefulness of the osmotic systems. That is, it now has been unexpectedly discovered that a novel dosage form manufactured as an osmotic device can be provided to deliver a bio-affecting drug at a fast rate and deliver a bio-affecting drug at a slow rate in a substantially constant dose over a prolonged period of time. By providing a fast rate of delivery the dosage form makes drug available early in the delivery period and essentially eliminates the start-up time associated with the prior art osmotic dosage forms. The dosage form by providing a slow rate of delivery also makes available drug delivery at a controlled and constant rate over a prolonged period of time. The dosage form made available by this invention uniquely embodies delivery at two different rates, thereby functioning according to a pre-selected, built-in optimal program of drug presentation.